CD19 and intraglandular CD163-positivity as prognostic indicators of pregnancy outcome in CD138-negative women with a previous fresh-embryo-transfer failure

J Reprod Immunol. 2021 Sep:147:103362. doi: 10.1016/j.jri.2021.103362. Epub 2021 Aug 26.

Abstract

Many factors impede embryonic implantation, and excluding obvious known factors such as chronic endometritis, the immune status of the endometrium may be related to pregnancy. Although an abundantly large number of immune cells infiltrate the endometrium during the secretory phase, whether these immune cells can be used as a predictor of prognosis in ART has not yet been clarified. In the present study we therefore retrospectively analyzed 97 CD138-negative women with a previous fresh-embryo-transfer failure. We assessed the expression of CD56+ uNK cells, CD16+ NK cells, CD57+ NK cells, CD68+ pan-macrophages, CD163+ M2 macrophages, CD4+T cells, CD8+T cells, FOXP3+ regulatory T cells, and CD19+ B cells in the endometrium by IHC to evaluate mid-luteal endometrial immune cells as prognostic indicators of pregnancy outcome in the next frozen-embryo-transfer cycle. CD19-positive cells and the intraglandular CD163-positivity rate increased significantly in the clinically non-pregnant group (0.47 % vs. 0.20 %, P = 0.021; 61 % vs. 30 %, P = 0.017). The ratios of CD4/CD8 were also higher in the non-pregnant group (1.96 vs. 1.45, P = 0.005).The area under the ROC curve of CD19 cell number alone, the intraglandular CD163-positivity alone, and CD19 number combined with the intraglandular CD163-positivity were 0.692 (95 % CI, 0.55-0.834), 0.661 (95 % CI, 0.514-0.809), and 0.748 (95 % CI, 0.614-0.882), respectively. The optimal cut-off value of CD19 was 0.464 %, and the clinical pregnancy rate and live-birth rate diminished significantly when the CD19 level was above this cut-off value. Our study suggests that CD19-positive cells and intraglandular CD163-positivity can be used as prognostic indicators of pregnancy outcome in CD138-negative patients who experienced first-fresh-embryo transfer failure.

Keywords: B cell; CD163; CD19; Endometrial immune cells; Implantation failure; Macrophages.

MeSH terms

  • Adult
  • Antigens, CD / analysis*
  • Antigens, CD / metabolism
  • Antigens, CD19 / analysis
  • Antigens, CD19 / metabolism
  • Antigens, Differentiation, Myelomonocytic / analysis*
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Embryo Implantation / immunology*
  • Embryo Transfer / methods*
  • Embryo Transfer / statistics & numerical data
  • Endometrium / immunology*
  • Endometrium / metabolism
  • Female
  • Humans
  • Infertility, Female / immunology
  • Infertility, Female / therapy*
  • Pregnancy
  • Pregnancy Outcome
  • Prognosis
  • Receptors, Cell Surface / analysis*
  • Receptors, Cell Surface / metabolism
  • Reference Values
  • Retrospective Studies
  • Treatment Failure
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, CD19
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • CD19 molecule, human
  • Receptors, Cell Surface